The search for other drugs that work like clozapine without the harmful side effects has resulted in a new group of medications to treat schizophrenia—also considered atypical antipsychotics. They typically cause fewer side effects than traditional antipsychotics, including a lower risk of tardive dyskinesia (TD; a disorder characterized by involuntary movements) and agranulocytosis. Like clozapine, they help control negative symptoms, and patients tend to comply with their use.

This newer group of drugs includes the following:

  • Aripiprazole (Abilify, generics)
  • Asenapine (Saphris; approved in 2009 to treat bipolar I in adults)
  • Risperidone (Risperdal)
  • Olanzapine (Zyprexa)
  • Quetiapine (Seroquel)
  • Ziprasadone (Zeldox, Geodon)
  • Paliperidone (Invega; approved in 2006 for adults and 2011 for adolescents 12 to 17; Invega Sustenna)
  • Lurasidone HCl (Latuda; approved in 2010)
  • Brexpiprazole (Rexulti; approved in 2015, also approved as an add-on drug to antidepressants to treat major depressive disorder)
  • Cariprazine (Vraylar; approved by the FDA in September 2015, also approved to treat bipolar disorder)

These drugs control psychosis by blocking dopamine D2 receptors and the serotonin 5HT2 receptors in the brain. The addition of a serotonin blocker may be what boosts their efficacy.

The following are common side effects for these medications:

  • Aripiprazole
    • Headache
    • Nausea
    • Restlessness accompanied with anxiety and agitation (called acathisia or akathisia)
  • Asenapine
    • Decreased sensitivity in the mouth
    • Drowsiness
    • Inability to remain still or motionless
  • Risperidone
    • Agitation
    • Anxiety
    • Headache
    • Insomnia
    • Muscle tremor
  • Olanzapine
    • Drowsiness
    • Headache
    • Insomnia
    • Nasal congestion
    • Weight gain
    • Post-injection delirium sedation (PDSS; the drug carries a boxed warning for this serious side effect)
  • Quetiapine
    • Dizziness and vertigo
    • Drowsiness
    • Headache
  • Brexpiprazole
    • Weight gain
    • Restlessness
  • Cariprazine
    • Extrapyramidal symptoms (e.g., tremor, slurred speech, involuntary muscle movements)

Studies have indicated that ziprasadone may produce less weight gain and fewer metabolic side effects (e.g., insulin resistance) than other medications. Side effects include excessive sleepiness (somnolence), nausea, dizziness, and upper respiratory infection.

At this time, there are no established risks associated with the use of antipsychotic drugs during pregnancy. However, clinical research involving pregnant women is lacking. Women are advised to discuss the benefits and risks with their physician, especially during and after pregnancy, since these drugs are excreted in breast milk. They also should not be used in older adults with dementia-related psychoses.

In May 2009, the U.S. Food and Drug Administration approved loperidone (Fanapt) to treat adults with schizophrenia. Side effects associated with this medication include the following:

  • Congestion
  • Dizziness
  • Drowsiness
  • Dry mouth
  • Fatigue
  • Rapid heart rate (tachycardia)
  • Sudden, severe drop in blood pressure (orthostatic hypotension)
  • Weight gain

Paliperidone, which was approved in 2006 to treat schizophrenia in adults and in April 2011 to treat adolescents with the disorder, may cause excessive sleepiness, restlessness, headache and insomnia.

Side effects associated with Lurasidone HCl (Latuda), which was approved by the FDA in 2010 to treat schizophrenia in adults, include the following:

  • Abnormal movements (e.g., tremors, slow or stiff movement)
  • Agitation
  • Drowsiness
  • Restlessness, inability to be still or motionless (akathisia)
  • Nausea

Publication Review By: Stanley J. Swierzewski, III, M.D.

Published: 31 Jan 2001

Last Modified: 02 Oct 2015